Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial.

The lancet. Diabetes & endocrinology Pub Date : 2022-03-01 Epub Date: 2022-02-04 DOI:10.1016/S2213-8587(22)00008-0
Takashi Kadowaki, Joakim Isendahl, Usman Khalid, Sang Yeoup Lee, Tomoyuki Nishida, Wataru Ogawa, Kazuyuki Tobe, Toshimasa Yamauchi, Soo Lim
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In the Semaglutide Treatment Effect in People with obesity (STEP) 6 trial, we assessed the effect of semaglutide versus placebo for weight management in adults from east Asia with obesity, with or without type 2 diabetes.</p><p><strong>Methods: </strong>This randomised, double-blind, double-dummy, placebo-controlled, phase 3a superiority trial was done at 28 outpatient clinics in Japan and South Korea. Eligible participants were adults (aged ≥18 years in South Korea; ≥20 years in Japan) with a BMI of at least 27·0 kg/m<sup>2</sup> with two or more weight-related comorbidities or a BMI of 35·0 kg/m<sup>2</sup> or more with one or more weight-related comorbidity (one comorbidity had to be either hypertension, dyslipidaemia, or, in Japan only, type 2 diabetes) who had at least one self-reported unsuccessful dietary attempt to lose bodyweight. Participants were randomly assigned (4:1:2:1) to once-weekly subcutaneous semaglutide 2·4 mg or matching placebo, or semaglutide 1·7 mg or matching placebo, plus lifestyle recommendations for 68 weeks. Data for the placebo groups were pooled in statistical analyses. The primary endpoints were percentage change in bodyweight from baseline at week 68 and the proportion of participants who had achieved a reduction of at least 5% of baseline bodyweight at week 68. Change in abdominal visceral fat area was assessed as a supportive secondary endpoint using computed tomography scanning in a subset of participants. Efficacy outcomes were assessed in the full analysis set, which included all randomly assigned participants according to the intention-to-treat principle. Safety was assessed in all participants who received at least one dose of the study drug. 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引用次数: 60

Abstract

Background: Semaglutide 2·4 mg once weekly has been investigated for weight management in global populations. Differences exist between Asian and non-Asian populations in terms of body composition and definitions of obesity. In the Semaglutide Treatment Effect in People with obesity (STEP) 6 trial, we assessed the effect of semaglutide versus placebo for weight management in adults from east Asia with obesity, with or without type 2 diabetes.

Methods: This randomised, double-blind, double-dummy, placebo-controlled, phase 3a superiority trial was done at 28 outpatient clinics in Japan and South Korea. Eligible participants were adults (aged ≥18 years in South Korea; ≥20 years in Japan) with a BMI of at least 27·0 kg/m2 with two or more weight-related comorbidities or a BMI of 35·0 kg/m2 or more with one or more weight-related comorbidity (one comorbidity had to be either hypertension, dyslipidaemia, or, in Japan only, type 2 diabetes) who had at least one self-reported unsuccessful dietary attempt to lose bodyweight. Participants were randomly assigned (4:1:2:1) to once-weekly subcutaneous semaglutide 2·4 mg or matching placebo, or semaglutide 1·7 mg or matching placebo, plus lifestyle recommendations for 68 weeks. Data for the placebo groups were pooled in statistical analyses. The primary endpoints were percentage change in bodyweight from baseline at week 68 and the proportion of participants who had achieved a reduction of at least 5% of baseline bodyweight at week 68. Change in abdominal visceral fat area was assessed as a supportive secondary endpoint using computed tomography scanning in a subset of participants. Efficacy outcomes were assessed in the full analysis set, which included all randomly assigned participants according to the intention-to-treat principle. Safety was assessed in all participants who received at least one dose of the study drug. This trial was registered with ClinicalTrials.gov, NCT03811574.

Findings: Between Jan 21, 2019 and June 4, 2019, 437 participants were screened, of whom 401 were randomly assigned to semaglutide 2·4 mg (n=199), semaglutide 1·7 mg (n=101), or placebo (n=101) and included in the intention-to-treat analysis. Estimated mean change in bodyweight from baseline to week 68 was -13·2% (SEM 0·5) in the semaglutide 2·4 mg group and -9·6% (0·8) in the semaglutide 1·7 mg group versus -2·1% (0·8) in the placebo group (estimated treatment difference [ETD] -11·1 percentage points [95% CI -12·9 to -9·2] for semaglutide 2·4 mg vs placebo; -7·5 percentage points [95% CI -9·6 to -5·4] for semaglutide 1·7 mg vs placebo; both p<0·0001). At week 68, a larger proportion of participants had achieved a 5% or higher reduction in baseline bodyweight in the semaglutide 2·4 mg group (160 [83%] of 193 participants) and semaglutide 1·7 mg group (71 [72%] of 98 participants) than in the placebo group (21 [21%] of 100 participants); odds ratio [OR] 21·7 [95% CI 11·3 to 41·9] for semaglutide 2·4 mg vs placebo; OR 11·1 [95% CI 5·5 to 22·2] for semaglutide 1·7 mg vs placebo; both p<0·0001). Abdominal visceral fat area was reduced by 40·0% (SEM 2·6) among participants in the semaglutide 2·4 mg group and 22·2% (3·7) among participants in the semaglutide 1·7 mg group versus 6·9% (3·8) in the placebo group (ETD -33·2% [95% CI -42·1 to -24·2] for semaglutide 2·4 mg vs placebo; -15·3% [95% CI -25·6 to -4·9] for semaglutide 1·7 mg vs placebo). 171 (86%) of 199 participants in the semaglutide 2·4 mg group, 82 (82%) of 100 participants in the semaglutide 1·7 mg group, and 80 (79%) of 101 participants in the placebo group reported adverse events. Gastrointestinal disorders, which were mostly mild to moderate, were reported in 118 (59%) of 199 participants in the semaglutide 2·4 mg group, 64 (64%) of 100 participants in the semaglutide 1·7 mg group, and 30 (30%) of 101 participants in the placebo group. Adverse events leading to trial product discontinuation occurred in five (3%) of 199 participants in the semaglutide 2·4 mg group, three (3%) of 100 participants in the semaglutide 1·7 mg group, and one (1%) of 101 participants in the placebo group.

Interpretation: Adults from east Asia with obesity, with or without type 2 diabetes, given semaglutide 2·4 mg once a week had superior and clinically meaningful reductions in bodyweight, and greater reductions in abdominal visceral fat area compared with placebo, representing a promising treatment option for weight management in this population.

Funding: Novo Nordisk.

Translations: For the Korean and Japanese translations of the abstract see Supplementary Materials section.

每周一次西马鲁肽治疗东亚人群中超重或肥胖、伴有或不伴有2型糖尿病的成年人(step6):一项随机、双盲、双虚拟、安慰剂对照的3a期试验。
背景:在全球人群中研究了每周一次的西马鲁肽2.4 mg用于体重管理。亚洲人和非亚洲人在身体组成和肥胖定义方面存在差异。在塞马鲁肽对肥胖患者的治疗效果(STEP) 6试验中,我们评估了塞马鲁肽与安慰剂对东亚肥胖、伴或不伴2型糖尿病的成人体重管理的效果。方法:这项随机、双盲、双假、安慰剂对照的3a期优势试验在日本和韩国的28家门诊诊所进行。符合条件的参与者为成年人(韩国年龄≥18岁;≥20岁(日本),BMI≥27.0 kg/m2,伴有两种或两种以上体重相关合并症,或BMI≥35.0 kg/m2,伴有一种或多种体重相关合并症(其中一种合并症必须是高血压、血脂异常,或(仅在日本)2型糖尿病),至少有一次自我报告的饮食减肥尝试不成功。参与者被随机分配(4:1:2:1),每周一次皮下注射塞马鲁肽2.4 mg或匹配安慰剂,或塞马鲁肽1.7 mg或匹配安慰剂,加上68周的生活方式建议。安慰剂组的数据汇总在统计分析中。主要终点是在第68周时体重从基线变化的百分比,以及在第68周时体重减少至少5%的参与者的比例。在一部分参与者中,使用计算机断层扫描评估腹部内脏脂肪面积的变化作为辅助次要终点。疗效结果在完整的分析集中进行评估,其中包括根据意向治疗原则随机分配的所有参与者。对所有接受至少一剂研究药物的参与者进行了安全性评估。该试验已在ClinicalTrials.gov注册,编号NCT03811574。结果:在2019年1月21日至2019年6月4日期间,筛选了437名参与者,其中401名随机分配到semaglutide 2.4 mg (n=199), semaglutide 1.7 mg (n=101)或安慰剂(n=101),并纳入意向治疗分析。从基线到第68周体重的估计平均变化在semaglutide 2.4 mg组为- 13.2% (SEM为0.5),semaglutide 1.7 mg组为- 9.6% (SEM为0.8),而安慰剂组为- 2.1% (0.8%)(semaglutide 2.4 mg与安慰剂的估计治疗差异[ETD] - 11.1个百分点[95% CI为- 12.9至- 9.2];semaglutide 1.7 mg vs安慰剂- 7.5个百分点[95% CI - 9.6 ~ - 5.4];结论:与安慰剂相比,来自东亚的肥胖成年人,无论有无2型糖尿病,给予西马鲁肽2.4 mg,每周1次,体重减轻明显且具有临床意义,腹部内脏脂肪面积减少更大,代表了这一人群体重管理的有希望的治疗选择。融资:诺和诺德。翻译:有关摘要的韩文和日文翻译,请参阅补充资料部分。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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